title: Dissociation of β-amyloid from lipoprotein in cerebrospinal fluid from Alzheimer's disease accelerates β-amyloid-42 assembly.
abstract: Monoclonal 2C3 specific to β-amyloid (Aβ) oligomers (AβOs) enabled us to test our hypothesis that the alteration of lipoprotein-Aβ interaction in the central nervous system (CNS) initiates and/or accelerates the cascade favoring Aβ assembly. Immunoprecipitation of frontal cortex employing 2C3 unequivocally detected soluble 4-, 8-, and 12-mers in Alzheimer's disease (AD) brains. Immunoblot analysis of the entorhinal cortex employing 2C3 revealed that the accumulation of soluble 12-mers precedes the appearance of neuronal loss or cognitive impairment and is enhanced as the Braak neurofibrially tangle (NFT) stages progress. The dissociation of soluble Aβ from lipoprotein particles occurs in cerebrospinal fluid (CSF), and the presence of lipoprotein-free oligomeric 2C3 conformers (4- to 35-mers) was evident, which mimic CNS environments. Such CNS environments may strongly affect conformation of soluble Aβ peptides, resulting in the conversion of soluble Aβ(42) monomers into soluble Aβ(42) assembly. The findings suggest that functionally declined lipoproteins may accelerate the generation of metabolic conditions leading to higher levels of soluble Aβ(42) assembly in the CNS.
authors.affiliation: Department of Alzheimer's Disease Research, Research Institute, National Center for Geriatrics and Gerontology, Aichi, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Takamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawarabayashi
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Yokoseki
authors.forename: Masao
authors.initials: M
authors.lastname: Shibata
authors.forename: Maho
authors.initials: M
authors.lastname: Morishima-Kawashima
authors.forename: Yuko
authors.initials: Y
authors.lastname: Saito
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murayama
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ihara
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
authors.forename: Makoto
authors.initials: M
authors.lastname: Michikawa
authors.forename: Etsuro
authors.initials: E
authors.lastname: Matsubara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000704:Analysis of Variance; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D008074:Lipoproteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)